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The song's title refers to the drunken haze in which the narrator has existed while spending an entire season at a beach resort community. The three verses describe his day-to-day activities. He passes his time playing guitar on his front porch and watching tourists sunbathe, all the while eating sponge cake and waiting for a pot of shrimp to boil. He has nothing to show for his time except a tattoo of a woman that he cannot remember having done. While out for a walk, he cuts his heel and returns home to ease his pain with a fresh batch of margaritas.

The three choruses reveal that the narrator is drowning his sorrows over a failed romance, and his friends are telling him that his former girlfriend is at fault. The last line of each shows his shifting attitude toward the situation: "it's nobody's fault," then "hell, it could be my fault," and finally "it's my own damn fault."

Buffett revealed during the recording of an episode of CMT's Crossroads with the Zac Brown Band that "Margaritaville" was actually supposed to be performed by Elvis Presley, but Elvis died the year that the song was released. Buffett got to perform it instead.[6]

There is a "lost verse" to this song, as described by Buffett, which he often adds when performing in concert, which was reputedly edited out before recording the song in order to make the song more airplay-friendly. The song was shortened even further for the radio edit.

There is some confusion as to whether Buffett sings "Wasted away"[7] or "Wastin’ away" in the chorus of the song. The original unedited lyrics, that appear on the record sleeve to the Changes in Latitudes, Changes in Attitudes LP, read "Waistin'" [sic].[8] Also, most guitar tablature and sheet music read "Wastin'." Buffett has never made a statement on the issue. However, he has also been known to use "wasted" in some performances, as well as in the video game re-recording for Rock Band.

A radio edit was released in 1977, timing at 3:20. The abridged version omits:

The interlude between the second chorus and third verse.

The section during the third chorus and final refrain "…woman to blame but I know, it's my own damn fault. Yes and, some people claim that there's a…" This makes the song structure riff-verse-chorus-verse-chorus-verse-chorus-riff, as opposed to riff-verse-chorus-verse-chorus-interlude-verse-chorus-refrain-riff.

The track itself was sped up a half-step. The original recording of the key of D would be E-flat.

In 2006, Kenan Thompson did a parody of the song on a Weekend Update sketch on Saturday Night Live where he plays a soldier who found out he was going to the U.S.-Mexico border rather than Baghdad. When Amy Poehler asks him what his reaction was when he discovered he was going to the border, in the next shot, he has a Corona banner above him, a sombrero on his head. He is swaying a Corona beer bottle and singing, "Wasting away again not in Iraq." This was likely a parody on Mortaritaville, which was recorded around 2 years prior.[9] In the show Napoleon Dynamite, Kip mentions that the animatronics at Goof Nutz Pizza sing the song "Pizzaritaville."

In 1991 comedian Mark Eddie, along with Carlo Volhl wrote a parody song titled, "Marijuanaville". The song appeared on the album Rock & Roll Comedy Cuts Part I. Many people wrongly attribute the parody version to other artists like, Tom Petty, Tenacious D, Insane Clown Posse and Dan Fogelberg. This was recently addressed by Mark Eddie in a YouTube video.

Jimmy Buffett's Margaritaville, a casual diningrestaurant chain, tourist destination and chain of stores (shops) selling Buffett-themed franchise merchandise in Jamaica, Mexico and the U.S. In 1985, Buffett opened a "Margaritaville" restaurant in Key West, though his first was in Orange Beach, Alabama.